Myocardial Remodeling in Hypertensive Ren-2 Transgenic Rats

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Abstract
Abstract Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin. We determined the extent of left ventricular remodeling present in Ren-2 rats at 16 weeks of age by measuring blood pressure, ratio of heart weight to body weight, left ventricular wall thickness, passive (diastolic) left ventricular compliance, and left ventricular collagen content using hydroxyproline and collagen area fraction. Changes in perivascular fibronectin and collagen type I and III were examined with immunohistochemistry. Blood pressure values at time of death were 244±15 mm Hg for Ren-2 rats (mean±SD, n=5). Ratios of heart weight to body weight (grams per kilogram) for Ren-2 animals were 4.1±0.2 versus 3.1±0.1 for controls (n=6, P <.001). Wall thickness values for control animals were 2.6±0.1 versus 4.1±0.4 mm for Ren-2 animals ( P <.001). Left ventricular Ren-2 hydroxyproline measurements were significantly decreased (3.4±0.2 versus 4.7±0.9 mg/g dry wt for controls). Significant decreases of approximately 30% were also observed in collagen area fraction in Ren-2 rats. Immunohistochemical and picrosirius red staining indicated increased amounts of perivascular fibrosis in all Ren-2 animals (when compared with controls) with enhanced levels of perivascular fibronectin and type I and type III collagen proteins. Left ventricular compliance measurements indicated a decrease in left ventricular volume for all left ventricular pressures ( P =.07). In conclusion, Ren-2 animals at 16 weeks of age demonstrated a substantial degree of cardiac hypertrophy that was accompanied by perivascular but not diffuse fibrosis and a stiffened left ventricle.